Comprehensive Analysis of Alternative Splicing Across Tumors from 8,705 Patients

Academic Article


  • Our comprehensive analysis of alternative splicing across 32 The Cancer Genome Atlas cancer types from 8,705 patients detects alternative splicing events and tumor variants by reanalyzing RNA and whole-exome sequencing data. Tumors have up to 30% more alternative splicing events than normal samples. Association analysis of somatic variants with alternative splicing events confirmed known trans associations with variants in SF3B1 and U2AF1 and identified additional trans-acting variants (e.g., TADA1, PPP2R1A). Many tumors have thousands of alternative splicing events not detectable in normal samples; on average, we identified ≈930 exon-exon junctions (“neojunctions”) in tumors not typically found in GTEx normals. From Clinical Proteomic Tumor Analysis Consortium data available for breast and ovarian tumor samples, we confirmed ≈1.7 neojunction- and ≈0.6 single nucleotide variant-derived peptides per tumor sample that are also predicted major histocompatibility complex-I binders (“putative neoantigens”). A pan-cancer analysis by Kahles et al. shows increased alternative splicing events in tumors versus normal tissue and identifies trans-acting variants associated with alternative splicing events. Tumors contain neojunction-derived peptides absent in normal samples, including predicted MHC-I binders that are putative neoantigens.
  • Published In

  • Cancer Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Kahles A; Lehmann KV; Toussaint NC; Hüser M; Stark SG; Sachsenberg T; Stegle O; Kohlbacher O; Sander C; Caesar-Johnson SJ
  • Start Page

  • 211
  • End Page

  • 224.e6
  • Volume

  • 34
  • Issue

  • 2